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Human Studies
Reprogramming of Human Mature Adult Cells to Pluripotent Stem Cells by Cell Surface Contact

Nuclear transfer or cloning technology, such as the one that gave rise to Dolly the sheep, is one method of reprogramming the differentiation of  mature adult cells. Via this process, a mature adult cell is converted into a pluripotent stem cell that is capable of giving rise to all of the more than the 200 different specialised cell types that make up an organism.

The work of Dr Ilham Saleh Abuljadayel published  in June 2003 in Current Medical Research and Opinion (CMRO 2003; 19(5): 355-375) (http://www.cmrojournal.com) describes for the first time how mature adult cells obtained from human blood can be reprogrammed by cell surface contact to become pluripotent stem cells. This process which she has termed “retrodifferentiation’’ demonstrates the ex vivo production of a variety of pluripotent stem cell types such as haematopoietic, neuronal and cardiomyogenic cells from white blood cells obtained from healthy blood donors. The process was achieved by exposing the cells to a specific antibody. 

Dr Abuljadayel has also shown that, from a single blood donor, a plentiful supply of pluripotent stem cells can be generated within a very short period of time. These can be redifferentiated into either blood cells, beating heart cells , neurones, glia, oligodendrocytes or embryonic stem cells capable of forming the three germ layers, the constituent of a developing embryo. What’s more, the in vivo functional utility of the pluripotent stem cells has been demonstrated in an immunodeficient animal model in which engraftment in primary and secondary lymphoid organs was observed. Another indicator of such cells’ therapeutic potential is the fact that  neurons produced in this manner have been shown to secrete dopamine and serotonin, the former being an important player in the reversal of Parkinson’s disease. Neuronal stem cells could also be important in repairing spinal cord injury and motor neuron disorders such as amyotrophic lateral sclerosis (ALS).

 The technology offers a viable option for the generation of large numbers of pluripotent stem cells. These are likely to have many potential applications in the clinic. The source material is blood: the most accessible tissue in our body when compared to other solid tissues and organs. This fluid tissue can be extracted by simple venipuncture or aphaeresis. The procedure raises no ethical concerns and removes the need to resort to embryos and aborted foetuses. The technology is also cost-effective, producing relatively large quantities of stem cells within a short time, which could eventually save lives and shorten patient waiting lists.

 The process can be applied in either autologous or allogeneic settings. Autologous donation  eliminates any immune rejection i.e. graft-versus-host disease whilst allogeneic donation may be useful for mounting a donor-derived antitumour response and for the treatment of genetic diseases e.g. sickle cell anaemia, congenital heart disorder.

 Doctor Abuljadayel is currently Chief Scientific Officer of TriStem Corporation Limited, a private biotechnology company that owns a UK-based subsidiary. Her work has arisen from over a decade of studies, during which the technology has been patented in many countries worldwide including the UK and USA. In Autumn 2001, she was invited to submit evidence to the House of Lords Select Committee for Stem Cell Research as part of their document that was released February 27th 2002. For potential application in the clinic TriStem is currently completing the automation of this novel process in collaboration with PA consulting group a leading global management and technology consulting firm. TriStem also plan to sell the stem cells produced through its patented technology for research purposes in the near future.

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